Transforming growth factors (TGF's) are EGF-related peptides which have been isolated froma variety of rodent and human tumors and from the conditioned medium of rodent and human carcinoma cell lines and from retorvirus transformed cells. TGF's are able to reversibly confer upon normal cells certain properties associated with the transformed phenotype namely a reduced serum requirement for growth and a loss of anchorage-dependent growth. TGF's have recently been isolated from rat mammary adenocarcinomas. These TGF's are: 1. able to compete with EGF for receptor binding; 2. induce the anchorage-independent growth of mouse and rat fibroblasts in soft agar; 3. reduce the serum requirement and function as potent mitogens for fibroblasts and normal mammary epithelial cells in monolayer culture and 4. differentially stimulate collagen production in both epithelial and mesenchymal cells. The rodent mammary TGF's have a molecular weight of 68,000 and a pI of 5.9. Comparable, but as yet not fully characterized, activities have been isolated from several human breast tumor samples, a transplantable human mammary tumor and in the conditioned medium of a human mammary carcinoma cell line (MCF-7) and several clones derived from this line. The activity in human breast tumor samples differ from the rat mammary TGF in that this activity has a pI of 4.9. Kirsten transformed mouse 3T3 cells provide a useful system in which to study the production of TGF's and to relate its production to the expression of the viral onc gene protein, p21. Cellular revertants of Kirsten transformed 3T3 cells have been isolated (C1 and F2) which possess 2 genomic copies of the v-kis sequences; express elevated levels of p21 but are no longer transformed or tumorigenic. The revertants, however, like the parental transformed calls lack detectable EGF receptors and secrete into the culture medium TGF as detected by the ability of conditioned medium concentrates to: 1. inhibit EGF binding to 3T3 cells; 2. stimulate the growth of fibroblasts in soft agar as colonies and 3, differentially stimulate the production of collagen. These results suggest that the lesions(s) in revertants are distal to the expression of p21 or the production of TGF.